MEK/ERK signaling pathway in apoptosis of SW620 cell line and inhibition effect of resveratrol

Objective:To study the involvement of MAPK MEK/ERK signaling transduction pathway in the apoptosis process of SW620 tumor cell line and the inhibition effect of resveratrol.Methods:SW620 cell lines were divided into 5 groups,namely,control group.PD98059 group,low-dose resveratrol group,mid-dose resveratrol group and high-dose resveratrol group.The inhibition rate of cell proliferation was detected by MTT method.The expression of apoptotic molecules and MEK/ERK signaling pathway related proteins were assayed by realtime PCR and Western blotting.Results:Compared with control group,the proliferation of cells treated with resveratrol was significantly inhibited.In the case of apoptotic molecules,the expression of Bax,Caspase 3 and Caspase 9 was increased significantly while the expression of anti-apoptotic molecule Bcl2 was decreased significantly in resveratrol groups with a dosedependent manner.In the case of molecules in MEK/ERK signaling pathway,the expression of Ras,Raf,MEK and ERKl/2 was decreased significantly in resveratrol groups with a dose-dependent manner.Conclusions:PD98059 and resveratrol can effectively inhibit the proliferation of SW620 through inhibiting the MEK/ERK signaling pathway.

Panax notogiseng saponin inhibits ischemia-induced apoptosis by activating PI3K/Akt signal pathway in cardiomyocytes

The panax notoginseng saponin(PNS) had been clinically used for the treatment of cardiovascular diseases and stroke in China.It had been demonstrated that PNS could protect cardiomyocytes from injury induced by ischemi- a,but the underlying molecular mechanisms of this protective effect were still unclear.This study was aimed to investigate the protective effect and molecular mechanisms of PNS on apoptosis in H9c2 cells in vitro and rat myocardial ischemia injury model in vivo.Annexin-V/PI assay shew that PNS could protect H9c2 cells from apoptosis induced by serum, glucose and oxygen deprivation(SGOD) in a dose-dependent manner.However,the anti-apoptotic effect of PNS was reversed by LY294002,a specific PI3K inhibitor.This antiapoptotic effect of PNS was confirmed by JC-1,a specific probe of mitochondrial membrane potential staining.PNS could significantly increase phos-Akt in H9c2 cells by Western blot assays and its effect could be inhibited by LY294002.Furthermore,PNS could improve ischemic-induced left ventricular function as reflected by EF,LVDd and LVDs.PNS could also inhibited cellular apoptosis in myocardial tissues in ischemic rats by TUNEL assay.PNS administration also increased the expression of phos-Akt in rat ischemic myocardial tissues.These results suggested that PNS could protect myocardial cells from apoptosis induced by ischemia in vitro model and in vivo model through activating-PI3K/Akt signal pathway which may be meaningful for further understanding the molecular mechanisms of cardiac protection of PNS.And the results might be useful in treatment of myocardial ischemia in future.

Inhibition of epidermal growth factor receptor signaling protects human malignant glioma cells from hypoxia - induced cell death

Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-

Down-regulation of HIV-1 Infection by Inhibition of the MAPK Signaling Pathway

The human immunodeficiency virus type 1(HIV-1) can interact with and exploit the host cellular machinery to replicate and propagate itself.Numerous studies have shown that the Mitogen-activated protein kinase(MAPK) signal pathway can positively regulate the replication of HIV-1,but exactly how each MAPK pathway affects HIV-1 infection and replication is not understood.In this study,we used the Extracellular signal-regulated kinase(ERK) pathway inhibitor,PD98059,the Jun N-terminal kinase(JNK) pathway inhibitor,SP600125,and the p38 pathway inhibitor,SB203580,to investigate the roles of these pathways in HIV-1 replication.We found that application of PD98059 results in a strong VSV-G pseudotyped HIV-1NL4-3 luciferase reporter virus and HIV-1NL4-3 virus inhibition activity.In addition,SB203580 and SP600125 also elicited marked VSV-G pseudotyped HIV-1 NL4-3 luciferase reporter virus inhibition activity but no HIV-1NL4-3 virus inhibition activity.We also found that SB203580 and SP600125 can enhance the HIV-1 inhibition activity of PD98059 when cells were treated with all three MAPK pathway inhibitors in combination.Finally,we show that HIV-1 virus inhibition activity of the MAPK pathway inhibitors was the result of the negative regulation of HIV-1 LTR promoter activity.

细菌与肿瘤的关系

人体携带有数以万亿计的细菌,其中大部分细菌与人体之间已经形成互惠互利的共生关系。细菌群落失调或者病原细菌感染会通过炎症以及分泌代谢物对人类健康产生负面影响,从而导致各种疾病的发生,这其中也包括肿瘤。细菌可以影响人体内肿瘤的发生发展,一方面细菌可以通过诱导慢性炎症、引起DNA损伤、激活核心致瘤信号通路等机制促进肿瘤的发生;另一方面又可以通过自身的溶瘤作用或者激活适应性免疫细胞来抑制肿瘤生长,此外通过基因工程修饰,一些被设计成低毒高效的药物输送的细菌已经成功地用在动物模型或临床试验中的肿瘤治疗。该文从细菌是如何促进肿瘤和肿瘤治疗上的应用两个方面综述近期有关细菌和肿瘤发生发展的相关文献,以期为肿瘤的治疗提供一种新的治疗思路。

幽门螺杆菌感染对胃黏膜上皮细胞病变的研究进展

通过系统阐述幽门螺杆菌在不同机制下通过诱导通路活性与胃黏膜上皮细胞病变的联系,从而探讨延缓胃黏膜上皮细胞恶性病变的新方法。通过对比胃黏膜上皮细胞病变过程中影响通路的不同发病机制,从而研究影响胃黏膜上皮细胞恶性病变的相关活性通路。大量研究证明,幽门螺杆菌感染通过细胞毒素相关基因A(CagA)依赖性和非依赖性机制引发诱导不同通路发挥作用。同时,在CagA依赖/非依赖性作用条件下,幽门螺杆菌可以通过作用于p53肿瘤抑制因子,从而促进胃黏膜上皮细胞发生恶变,是胃癌的重要致病原因之一。通过对胃黏膜上皮细胞与幽门螺杆菌相关作用的深入研究,找出延缓胃黏膜病变进展的作用机制,为临床上治疗幽门螺杆菌感染所致的一系列胃肠道疾病提供新思路。

广播电视无线发射中多径干扰的抑制技术研究

随着无线通信技术的飞速发展,传统的信号抑制技术已经无法满足日益复杂的通信需求。评述分集接收技术、均衡技术、扩频技术以及智能天线技术4种现有的无线通信抑制技术,深入分析它们的原理、应用及面临的挑战。阐述当前对新型抑制技术的研究,这些新技术有望在未来解决传统技术所面临的硬件复杂性、频谱资源限制和算法效率低等方面的问题。

TLR4/NF-κB/NLRP3通路抑制炎症反应作用的研究

Toll样受体(TLRs)是参与非特异性免疫的一类重要的蛋白质,是表达与固有免疫细胞最重要的模式识别受体之一,可识别来源于微生物的具有保守结构的分子,即病原体相关分子模式(PAMAs),从而激活机体产生免疫应答。核因子κB(NF-κB)在几乎所有类型的细胞和组织中都有表达,在调节对外部刺激的显著多样性的反应中起着关键作用,因此是多个生理和病理过程中的关键因素。而核苷酸结合寡聚化结构域样受体蛋白3(NLRP3),即NLRP3炎性小体通路在脑缺血再灌注和焦亡中具有重要意义,如NLRP3在脑缺血再灌注损伤时在小胶质细胞中被激活,随后在神经元和微血管内皮细胞中表达。由TLRs激活、NF-κB传递、NLRP3启动形成的TLR/NF-κB/NLRP3信号通路在机体各器官炎症反应中起到关键性作用,本文探讨了各类药物通过抑制该通路炎症反应,起到保护身体各大重要器官的作用。

Discovery of Chrysoeriol,a PI3K-AKT-mTOR Pathway Inhibitor with Potent Antitumor Activity against Human Multiple Myeloma Cells in vitro

This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3,and its related molecular mechanisms.Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay.CCK-8 assay was employed to examine the growth inhibition rate and IC 50 (48 h) in peripheral blood mononuclear cells (PBMNCs),RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations.Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE),and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software.The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC 50 concentration of chrysoeriol was adopted.The alterations in cell-cycle related proteins (Cyclin B1,Cyclin D1,p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis.The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol,resulting in cell cycle arrest in G 2 /M phase.Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein,meanwhile enhanced Cyclin B1 and p21 protein expression.Similar effects were not observed in PBMNCs from normal donors.It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor.It restrained the proliferation of human multiple myeloma cells,but didn’t affect proliferation of PBMNCs from normal donors.It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.

Is transcranial direct current stimulation a potential method for improving response inhibition?

Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area （pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase）. Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

基于PI3K/AKT信号通路探讨汉黄芩素对宫颈癌HeLa细胞移植瘤抑制作用影响

目的探究汉黄芩素对宫颈癌HeLa细胞移植瘤的抑制作用及机制。方法随机选取2018年1月—2020年12月常熟市中医院的50只Balb/c小鼠进行宫颈癌荷瘤模型造模,随机分为5组:模型对照组、阳性对照组、小剂量组、中剂量组及大剂量组。模型对照组不做特殊处理,阳性对照组腹腔注射25 mg/kg环磷酰胺,小剂量组、中剂量组、大剂量组小鼠灌胃25 mg/kg、50 mg/kg、100 mg/kg汉黄芩素。处死小鼠取出瘤体,比较各组肿瘤质量、体积,计算肿瘤生长抑制率;取出胸腺、脾脏并计算相关脏体指数。将小鼠肿瘤分为两份,一份采用伊红-美兰(HE)染色进行组织学观察;另一份采用免疫印迹法检测各组小鼠PI3K、AKT、p-AKT表达情况。结果阳性对照组的肿瘤生长抑制率为69.63%,大剂量组、中剂量组、小剂量组的肿瘤生长抑制率分别为77.78%、54.81%和31.85%均高于模型对照组,差异有统计学意义(P<0.05)。大剂量组肿瘤生长抑制率为77.78%高于阳性对照组,差异有统计学意义(P<0.05)。免疫印迹法结果显示,与模型对照组比较,大剂量组、中剂量组与小剂量组PI3K、AKT及p-AKT蛋白表达均显著降低,差异有统计学意义(P<0.05);高剂量组与阳性对照组PI3K、AKT和p-AKT表达量接近,差异有统计学意义(P<0.05)。结论汉黄芩素对宫颈癌Hela细胞移植瘤生长具有明显抑制作用,其作用机制可能通过抑制PI3K/AKT通路与诱导细胞凋亡有关。

Upregulated Ras/Raf/ERK1/2 signaling pathway:a new hope in the repair of spinal cord injury

An increasing number of studies report that the Ras/Raf/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway has a death-promoting apoptotic function in neural cells. We hypothesized that the Ras/Raf/ERK1/2 signaling pathway may be abnormally regulated in rat injured spinal cord models. The weight drop method was used to establish rat spinal cord injury at T9. Western blot analysis and immunohistochemical staining revealed Ras expression was dramatically elevated, and the phosphorylations of A-Raf, B-Raf and C-Raf were all upregulated in the injured spinal cord. Both mitogen-activated protein kinase kinase 1/2 and ERK1/2, which belong to the Ras/Raf signaling kinases, were upregulated. These results indicate that Ras/Raf/ ERK1/2 signaling may be upregulated in injured spinal cord and are involved in recovery after spinal cord injury.

紫铆素经EGFR-STAT3信号通路对荷宫颈癌裸鼠肿瘤生长的影响

目的探讨紫铆素对荷宫颈癌裸鼠肿瘤生长与肿瘤组织表皮生长因子受体(EGFR)、信号转导和转录激活因子3(signal transducer and activator of ranscription 3,STAT3)表达的影响。方法裸鼠左侧腑下接种宫颈癌SiHa细胞的方法构建宫颈癌模型,将成功构建的荷宫颈癌裸鼠随机分为模型组、阳性药组与低、中、高剂量组,每组各12只。低、中、高剂量组裸鼠分别给予11.5 mg/ml、46 mg/ml、115 mg/ml注射剂量的紫铆素注射,阳性药组给予4.3 ml/kg剂量的顺铂注射,模型组给予等量生理盐水;每天1次,连续注射7 d后,观察1周。测定各组裸鼠的抑瘤率及肝脏指数、肾脏指数;HE染色形态学观察肿瘤的病理特点,免疫组化、RT-qPCR检测肿瘤组织中EGFR、STAT3的表达水平。结果抑瘤率分析阳性药组(60.82±7.30%)和高剂量组(49.30±10.42)高于低、中剂量组,肿瘤体积与瘤重低于低、中剂量组和模型组;肾脏指数分析阳性药组(10.25±0.48)和高剂量组(10.13±0.47)低于模型组和低、中剂量组;EGFR蛋白表达阳性药组(0.002±0.002)、高剂量组(0.012±0.008)和STAT3蛋白表达阳性药组(0.063±0.011)、高剂量组(0.099±0.013)显著低于模型组和低、中剂量组;EGFR基因表达阳性药组(0.462±0.092)、高剂量组(0.524±0.115)和STAT3蛋白相对表达量阳性药组(0.435±0.123)、高剂量组(0.593±0.092)显著低于模型组和低、中剂量组;病理特点显示阳性药组、高剂量组肿瘤组织坏死情况较模型组和低、中剂量组明显降低;以上指标,差异有统计学意义(P<0.05)。结论紫铆素可有效抑制宫颈肿瘤的生长,且无明显毒性作用,其机制可能与宫颈肿瘤组织EGFR、STAT3表达相关。

基于动态轮廓曲线的运动图像特征识别研究

针对运动图像帧在识别过程中存在误差大,背景、纹理、边缘对运动目标轮廓边缘影响严重等问题,提出基于动态轮廓曲线的运动图像特征识别方法。首先采用不同大小的抑制强度值对图像轮廓的候选边缘进行处理,将有重叠的像素点加入组合中,通过组合结果,提高图像正确分类的概率,得出图像的轮廓边缘。然后对运动图像中相邻两帧间采用尺度变换,对得出新图像的像素值进行小波分解尺度逼近处理,得出收敛补偿,以Newmark迭代算法为基础,对预处理后的像素点进行提取。最后利用修复优化算法对像素点进行修复,通过拓扑梯度最小重构路径耦合修复方法对运动图像损坏区域进行识别,确定运动图像的拓扑梯度以及轮廓修复的关键点,当峰值信噪比为最大时,运动图像的轮廓像素点已修复完成。实验结果表明,采用所提方法对运动图像帧进行跟踪,帧的匹配度较高,跟踪性能良好,而且能够对图像的细节进行修复,修复效果显著。

阈下情绪启动对亚临床抑郁群体反应抑制的影响

目的:探究亚临床抑郁群体在无情绪任务下和阈下情绪启动条件下的反应抑制能力是否存在缺陷。方法:运用贝克抑郁量表(BDI-Ⅱ),流调中心用抑郁量表(CES-D)在山东某所普通高校筛选出亚临床抑郁群体组31名,健康对照组31名,通过停止信号范式与阈下情绪启动范式相结合的实验进行探究。结果:亚临床抑郁组和健康对照组在无情绪任务下的SSRT差异均不显著;在阈下情绪启动下停止信号任务中,亚临床抑郁组的SSRT显著大于健康对照组(F=4.310,P<0.05),亚临床抑郁组的GORT显著大于健康对照组(F=4.203,P<0.05)。结论:亚临床抑郁群体与正常人群的反应抑制能力在无情绪任务下没有差异,而在阈下情绪条件下亚临床抑郁群体对情绪材料的反应抑制存在缺陷。

紫草素诱导慢性髓系白血病细胞增殖抑制和凋亡的PTEN信号通路研究

目的:探讨紫草素对慢性髓系白血病K562细胞的作用及其可能机制。方法:体外培养慢性髓系白血病K562细胞,分组为对照组和紫草素10μmol/L组、紫草素30μmol/L组、紫草素50μmol/L组,分别培养12、24、48、72h后,MTT法检测细胞增殖抑制率,Annexin V FITC/PI染色结合流式细胞仪检测细胞凋亡率,同时用MTT法观察紫草素对K562细胞生长的影响;Western blot检测细胞内PTEN、p-PI3K和p-Akt蛋白表达。结果:紫草素能有效抑制K562细胞增殖,促进细胞凋亡,上调细胞PTEN蛋白表达量,下调p-PI3K和p-Akt蛋白表达量,各浓度间差异具有统计学意义(均P<0.05)。结论:紫草素能通过调控PTEN、p-PI3K、p-Akt信号通路抑制K562细胞的增殖,促进其凋亡。

穿心莲内酯抑制IKK/IκBα/NF-κB信号通路改善抑郁症大鼠的抑郁样行为

目的探讨穿心莲内酯(Andro)通过抑制核转录因子-κB抑制蛋白激酶(IKK)/核因子κB抑制蛋白(IκBα)/核因子-κB(NF-κB)信号通路改善抑郁症(MDD)大鼠的抑郁样行为。方法随机取12只SD大鼠作为空白对照组(NC组),其余大鼠采用慢性不可预知轻度应激(CUMS)结合孤养模式造模,将造模成功大鼠随机平分为模型组(Mod组)、Andro组(25 mg·kg^(-1)·d^(-1))、Res组(30 mg·kg^(-1)·d^(-1)IKK/IκBα/NF-κB信号通路激活剂Res)、Andro+Res组(25 mg·kg^(-1)·d^(-1)Andro+30mg·kg^(-1)·d^(-1)Res),每组12只大鼠,Mod组和NC组灌胃等量0.9%氯化钠溶液。旷场实验、糖水偏好实验、强迫游泳实验、平衡木实验评估大鼠行为;ELISA法检测血清IL-1β、IL-6、TNF-α水平;免疫荧光染色检测小胶质细胞、星形胶质细胞活性;Western blot检测NLRP3、cleaved-Caspase-1以及IKK/IκBα/NF-κB信号通路蛋白水平。结果与NC组相比,Mod组站立次数、饮用蔗糖量显著减少(P<0.05),游泳不动时间、通过平衡木时间、IL-1β、IL-6、TNF-α含量、Iba-1、GFAP阳性细胞数量、NLRP3、cleaved-Caspase-1、p-IKK/IKK、IκBα、p-NF-κB p65/NF-κB p65蛋白水平显著增加(P<0.05);与Mod组相比,Andro组大鼠游泳不动时间、通过平衡木时间、IL-1β、IL-6、TNF-α含量、Iba-1、GFAP阳性细胞数量、NLRP3、cleaved-Caspase-1、p-IKK/IKK、IκBα、p-NF-κB p65/NF-κB p65蛋白水平显著降低(P<0.05),站立次数、饮用蔗糖量显著增加(P<0.05),而Res组以上指标趋势相反(P<0.05);Res逆转了Andro对MDD大鼠抑郁样行为的改善。结论Andro可能通过下调IKK/IκBα/NF-κB通路对MDD大鼠的抑郁样行为起到一定的改善作用。

抑制核转录因子Gli1表达对人肺腺癌耐顺铂细胞株的顺铂耐药性逆转作用观察

目的观察抑制核转录因子Gli1表达对人肺腺癌耐顺铂细胞株的顺铂耐药性逆转作用。方法将人肺腺癌耐顺铂细胞株A549/DDP随机分为GANT61组、环杷明组、LY294002组、对照组,其中GANT61组加入10μmol/L的Gli1抑制剂GANT61,环杷明组加入10μmol/L的Smo抑制剂环杷明,LY294002组加入20μmol/L的PI3K抑制剂LY294002,对照组加入培养基。各组细胞继续培养48 h后,采用实时荧光定量PCR法和Western Boltting法检测细胞中Gli1 mRNA和蛋白,采用MTT法测算顺铂对各组细胞的半数抑制浓度(IC_(50)),采用Western Boltting法检测细胞中多药耐药相关蛋白(MRP1)及凋亡相关蛋白Bcl-2、Bax,采用Annexin V-FITC法测算各组细胞凋亡率。结果GANT61组、环杷明组、LY294002组、对照组细胞中Gli1 mRNA相对表达量分别为0.30±0.08、0.62±0.12、0.68±0.11、1.05±0.10,其中环杷明组与LY294002组相比,P>0.05;其余组间两两相比,P均<0.05。GANT61组、环杷明组、LY294002组、对照组细胞中Gli1蛋白相对表达量分别为0.28±0.12、0.59±0.07、0.55±0.13、0.97±0.06,其中环杷明组与LY294002组相比,P>0.05;其余组间两两相比,P均<0.05。顺铂对GANT61组、环杷明组、LY294002组、对照组细胞的IC_(50)值分别为(7.35±1.03)、(9.86±0.71)、(10.23±1.02)、(14.26±2.10)μg/mL,其中环杷明组与LY294002组相比,P>0.05;其余组间两两相比,P均<0.05。GANT61组、环杷明组、LY294002组、对照组MRP1蛋白的相对表达量分别为0.18±0.09、0.38±0.17、0.58±0.19、0.83±0.24,组间相比,P均<0.05。GANT61组、环杷明组、LY294002组、对照组细胞凋亡率分别为27.27%±0.99%、15.45%±1.01%、12.35%±1.80%、6.25%±0.38%,其中环杷明组与LY294002组相比,P>0.05;其余组间两两相比,P均<0.05。GANT61组、环杷明组、LY294002组、对照组细胞中Bcl-2蛋白的相对表达量分别为0.15±0.08、0.33±0.15、0.63±0.13、0.91±0.19,组间相比,P均<0.05。GANT61组、环杷明组、LY294002组、对照组细胞中Bax蛋白的相对表达量分别为1.88±0.38、1.34±0.25、1.27±0.39、0.64±0.18,其中环杷明组与LY294002组相比,P>0.05;其余组间两两相比,P均<0.05。结论抑制Gli1表达可通过降低顺铂对A549/DDP细胞的IC_(50)、促进A549/DDP细胞凋亡,逆转A549/DDP细胞对顺铂的耐药性;Smo抑制剂环杷明、PI3K抑制剂LY294002、Gli1抑制剂GANT61均可抑制A549/DDP细胞中Gli1的表达。

TROP2通过内质网钙铁离子交换影响胃癌侵袭的分子机制

目的探讨人滋养层细胞表面糖蛋白2(TROP2)通过内质网钙铁离子交换影响胃癌侵袭的分子机制。方法构建TROP2与PLOD2过表达/敲减细胞株,WB、RT-qPCR检测TROP2、PLOD2、磷脂酰肌醇4,5-二磷酸(PIP2)、胶原蛋白I型(COL-I)、缺氧诱导因子-1α(HIF-1α)、蛋白激酶C(PKC)mRNA和蛋白的表达水平,ELISA法检测三磷酸肌醇受体(IP3R)含量,比色分析法检测Fe^(2+)和Ca^(2+)含量。结果随着TROP2的表达量的变化,PLOD2、PIP2、IP3等蛋白水平随之同步变化,在PLOD2的过表达和敲减模型中,无论PLOD2如何变化,TROP2、PIP2、IP3R、PKC并无明显变化,但COL-I、HIF-1α随着PLOD2的变化同步增减。在离子水平,内质网Ca^(2+)浓度与TROP2和PLOD2的表达量呈正相关,Fe^(2+)浓度与TROP2和PLOD2的表达量呈负相关。结论PLOD2上游受TROP2的钙离子信号转导通路“内质网Ca^(2+)-Fe^(2+)交换”调控,下游通过调控HIF1α和胶原纤维交联促进肿瘤的侵袭、转移。

镜像神经元理论指导MOTOmed训练在脑卒中后肢体功能障碍的应用

目的:探讨镜像神经元理论指导MOTOmed训练对脑卒中后肢体功能障碍患者康复的影响。方法:选取2020年3月~2021年3月收治的96例脑卒中后肢体功能障碍患者,采用随机卡片号码法分为两组,对照组(n=48)开展以神经生理疗法、良肢位摆放、体位转移训练等项目的常规训练方案,研究组(n=48)开展基于镜像神经元理论指导的MOTOmed训练,均连续训练4周,分别使用Fugl-Meyer评分(FMA)、Berg平衡量表(BBS)、改良Ashworth评分量表(MAS)评估肢体功能障碍改善情况,评估康复训练前后两组患者躯干屈伸肌群肌电信号、大脑皮质运动区μ波Cz/CPz/CP3的脑电图信号变化情况。结果:治疗前,两组患者上肢FMA评分、下肢FMA评分差异无统计学意义(P>0.05);连续训练治疗4周后,研究组上肢FMA、下肢FMA评分均高于对照组(P<0.05)。治疗前,组间BBS评分、MAS评分及BI指数差异无统计学意义(P>0.05);治疗后,研究组BBS评分、BI指数高于对照组,且MAS评分低于对照组(P<0.05)。治疗前,组间健侧/患侧腹直肌、竖脊肌表面肌电信号差异无统计学意义(P>0.05);训练4周后,两组患者健侧两部位肌电信号均方根值均无明显变化(P>0.05),患侧两部位数值对比显示研究组显著高于对照组(P<0.05)。治疗前,组间Cz、CPz及CP3处μ波抑制指数差异无统计学意义(P>0.05);连续训练4周后,研究组3个电极处皮质μ波抑制指数均小于对照组(P<0.05)。结论:镜像神经元理论指导MOTOmed训练应用于脑卒中后肢体功能障碍可更好地改善患者躯体平衡能力和肢体运动功能,恢复躯干肌群肌力,抑制皮质运动区μ波,以重构神经系统。